Multiple myeloma is one of the hematological malignancies, accompanied by the clonal proliferation of plasma cells. Typical clinical symptoms of the patient with multiple myeloma are anemia, pathological bone fracture, hyper-calcemia, renal dysfunction, and reiterating infectious disease, which are caused by proliferation of malignant tumor cells in bone marrow. Chemotherapy or autologous bone marrow transplantation is adopted to prolong the patient's life. However, its prognosis is not satisfactory. Cause of multiple myeloma is yet to be elucidated due to its heterogeneity.
Lymphoma is a kind of hematopoietic tumor associated with abnormal proliferation of lymphoid cells. It is categorized into two classes, Hodgkin's disease with good prognosis and non-Hodgkin's lymphoma with bad prognosis. A new type of animal disease model is essential for new drug development.
Developing successful mouse disease model of human multiple myeloma and human T-cell lymphoma has been a challenge for investigating cause and developing treatment of those diseases for the long time. Several mouse models engrafted human myeloma cells have been reported. However, those methods were extremely complicated. For example, Pilarski et. al. engrafted human multiple myeloma cells into NOD/SCID mice by intra-cardiac injection (Non-patent reference 1). Yaccoby et. al. reported that a partially autonomous growth of human myeloma cells by implanting them into a small piece of human fetal bone, which was engrafted under a mouse skin. In the case of an experiment performed by Tsunenari, they reported about a new xenograft SCID mice model in which human KPMM2 myeloma was engrafted (Non-patent reference 2). However, KPMM2 has been already held in SCID mice as a form of solid tumor and their model does not necessarily represent the pathology of human myeloma. Accordingly, no humanized disease animal model, that can be easily used for the study of pathogenesis and therapy development, has been established based on the existing immune deficient mice.    Non-patent reference 1    Exp Haemat, 30, 221-228, 2002; Blood, 95, 1056-1065, 2000    Non-patent reference 2    Blood, 90, 2437-2444, 1997